Prognostic Value of an m6A RNA Methylation Regulator-Based Signature in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Recent researches have demonstrated that m6A methylation regulators play a key role in various cancers, such as gastric cancer and colon adenocarcinoma. Several m6A methylation regulators are reported to predict the prognosis of HCC. Therefore, there is a need to further identify the predictive value of m6A methylation regulators in HCC. We utilized The Cancer Genome Atlas (TCGA) database to obtain the gene expression profile of m6A RNA methylation regulators and clinical information for patients with HCC. Besides, we identified two clusters of HCC with various clinical factors by consensus clustering analysis. Then the least absolute shrinkage and selection operator (LASSO) and the Cox regression analysis were applied to construct a prognostic signature. Except for ZC3H13 and METTL14, a majority of the thirteen m6A RNA methylation regulators were significantly overexpressed in HCC specimens. HCC patients were classified into two groups (cluster 1 and cluster 2). The cluster 1 was with a significantly worse prognosis than cluster 2, and most of the 13 known m6A RNA methylation regulators were upregulated in cluster 1. Besides, we developed a prognostic signature consisting of YTHDF2, YTHDF1, METTL3, KIAA1429, and ZC3H13, which could successfully differentiate high-risk patients. More importantly, univariate and multivariate Cox regression analysis indicated that the signature-based risk score was an independent prognostic factor for patients with HCC. Our study showed these five m6A RNA methylation regulators can be used as practical and reliable prognostic tools of HCC, which might have potential value for therapeutic strategies.

Wu X ，Zhang X ，Tao L ，Dai X ，Chen P ... -  《-》

Comprehensive Analysis of PD-L1 Expression, Immune Infiltrates, and m6A RNA Methylation Regulators in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME). The transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail. Six m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells. Our study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.

Guo W ，Tan F ，Huai Q ，Wang Z ，Shao F ，Zhang G ，Yang Z ，Li R ，Xue Q ，Gao S ，He J ... -  《Frontiers in Immunology》

Multiple m(6)A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis.

Qu N ，Qin S ，Zhang X ，Bo X ，Liu Z ，Tan C ，Wen G ，Jiang H ... -  《BMC CANCER》

Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.

Deng M ，Fang L ，Li SH ，Zhao RC ，Mei J ，Zou JW ，Wei W ，Guo RP ... -  《-》

Identification of an eight-m6A RNA methylation regulator prognostic signature of uterine corpus endometrial carcinoma based on bioinformatics analysis.

N6-methyladenosine (m6A) methylation is proved to play a significant role in human cancers. This study aimed to explore the association between m6A ribonucleic acid (RNA) methylation regulators and uterine corpus endometrial carcinoma (UCEC), and build a prognostic signature of m6A regulators for UCEC.RNA-seq transcriptome data and clinicopathological data of UCEC were downloaded from the Cancer Genome Atlas database. We compared the expression of 23 m6A-regulators in tumor tissues and nontumor tissues. Then we classified the data into 3 clusters by consensus clustering analysis. Several regulators were picked out as the prognostic signature of patients with UCEC based on least absolute shrinkage and selection operator Cox regression analysis. Additionally, we established a predictive nomogram to calculate survival times. Finally, we used receiver operating characteristic curve, univariate Cox regression analysis, and multivariate Cox regression analysis to further verify the prognostic value of the risk signature consisting of m6A regulators.The expression of 18/23 m6A regulators was significantly different in UCEC compared with normal samples. Gene ontology functional analysis of these regulators revealed that they were mainly participated in RNA splicing, stabilization, modification, and degradation. LRPPRC, IGFBP2, KIAA1429, IGFBP3, FMR1, YTHDF1, METTL14, and YTHDF2 were selected to construct the risk signature and predictive nomogram. The results of receiver operating characteristic curve, univariate Cox regression analysis, and multivariate Cox regression analysis for the risk signature showed a good predictive performance for UCEC.The risk signature of 8-m6A regulators has potential prognostic value for patients with UCEC.

Miao C ，Fang X ，Chen Y ，Zhao Y ，Guo Q ... -  《-》